Two central problems in somatic cell genetics are 1) to increase the number of kinds of genes that can be analyzed; and 2) to increase the resolution with which individual genes and gene clusters can be analyzed. Three new approaches will be used to increase the number of genes studied: 1) Monoclonal antibodies will be used to define, map, and biochemically characterize cell surface antigens including virus receptors, differentiation antigens, and tumor antigens. 2) Two-dimensional gel electrophoresis will be used to enlarge the number of cellular polypeptides that can be studied. 3) Cloned DNA probes will allow "silent" genes to be detected. The second overall problem will be approached through studies of gene transfer mechanisms. Experiments will focus on the physical properties of the stable and unstable transgenomes, the role of carrier DNA in the formation of the transgenome, and the structural and functional relationships between the transgenome and "endogenous" genes following integration into a host chromosome. Together, these approaches will allow a concerted attack on the problems of the organization and function of the mammalian chromosome, ranging in degree of resolution from the level of chromosomal fragments to the level of nucleotide sequence.